Rb1 and Pten Co-Deletion in Osteoblast Precursor Cells Causes Rapid Lipoma Formation in Mice

PloS One
Emma A FiltzTimothy C Hallstrom

Abstract

The Rb and Pten tumor suppressor genes are important regulators of bone development and both are frequently mutated in the bone cancer osteosarcoma (OS). To determine if Rb1 and Pten synergize as tumor suppressor genes for osteosarcoma, we co-deleted them in osteoprogenitor cells. Surprisingly, we observed rapid development of adipogenic but not osteosarcoma tumors in the ΔRb1/Pten mice. ΔPten solo deleted mice also developed lipoma tumors but at a much reduced frequency and later onset than those co-deleted for Rb1. Pten deletion also led to a marked increase in adipocytes in the bone marrow. To better understand the function of Pten in bone development in vivo, we conditionally deleted Pten in OSX(+) osteoprogenitor cells using OSX-Cre mice. μCT analysis revealed a significant thickening of the calvaria and an increase in trabeculae volume and number in the femur, consistent with increased bone formation in these mice. To determine if Pten and Rb1 deletion actively promotes adipogenic differentiation, we isolated calvarial cells from Pten(fl/fl) and Pten(fl/fl); Rb1(fl/fl) mice, infected them with CRE or GFP expressing adenovirus, treated with differentiation media. We observed slightly increased adipogenic, and osteogenic di...Continue Reading

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Citations

Jul 15, 2020·Journal of Cutaneous Pathology·Andrea SagginiHeinz Kutzner
Mar 5, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Aaron L SarverTimothy C Hallstrom
Jul 18, 2021·The Journal of Biological Chemistry·Anna S KirsteinAntje Garten

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Methods Mentioned

BETA
PCR
genotyping
transgenic

Software Mentioned

NIH
CT Pro 3D
GraphPad Prism
VG Studio Max
ImageJ
SkyScan CT - Analyzer

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